Pontiac fever: an operational definition for epidemiological studies

BACKGROUND: Pontiac fever is usually described in epidemic settings. Detection of Pontiac fever is a marker of an environmental contamination by Legionella and should thereby call for prevention measures in order to prevent outbreak of Legionnaire's disease. The objective of this study is to propose an operational definition of Pontiac fever that is amenable to epidemiological surveillance and investigation in a non epidemic setting. METHODS: A population of 560 elderly subjects residing in 25 nursing homes was followed during 4 months in order to assess the daily incidence of symptoms associated, in the literature, with Pontiac fever. The water and aerosol of one to 8 showers by nursing home were characterized combining conventional bacterial culture of Legionella and the Fluorescence In Situ Hybridization (FISH) technique that used oligonucleotides probes specific for Legionellaceae. A definition of Pontiac fever was devised based on clinical symptoms described in epidemic investigations and on their timing after the exposure event. The association between incidence of Pontiac fever and shower contamination levels was evaluated to test the relevance of this definition. RESULTS: The proposed definition of Pontiac fever associated the following criteria: occurrence of at least one symptom among headache, myalgia, fever and shivers, possibly associated with other 'minor' symptoms, within three days after a shower contaminated by Legionella, during a maximum of 8 days (minimum 2 days). 23 such cases occurred during the study (incidence rate: 0.125 cases per person-year [95% CI: 0.122–0.127]). A concentration of Legionella in water equal to or greater than 10(4).L(-1 )(FISH method) was associated with a significant increase of incidence of Pontiac fever (p = 0.04). CONCLUSION: Once validated in other settings, the proposed definition of Pontiac fever might be used to develop epidemiological surveillance and help draw attention on sources of Legionella

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo